Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

NCT ID: NCT03489343

Last Updated: 2021-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-24
• Study Completion Date: 2020-06-03

Brief Summary

This was the first study to test Sym023 in humans. The primary purpose of this study was to see if Sym023 is safe and tolerable for patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.

Detailed Description

This study evaluated the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym023, a recombinant, fully human, anti-T-cell immunoglobulin and mucin-domain containing-3 (anti-TIM-3) monoclonal antibody (mAb). The goal was to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym023 when administered once every 2 weeks (Q2W) by intravenous (IV) infusion to patient cohorts with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available. If an MTD was not identified, a maximum administered dose (MAD) was to be determined. Sym023 was given to patients in escalating dose cohorts; each patient was given one fixed dose level.

Conditions

Metastatic Cancer; Solid Tumor; Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sym023 0.03 mg/kg

Sym023 was administered at a dose of 0.03 mg/kg by intravenous infusion

Group Type: EXPERIMENTAL

Sym023

Intervention Type: DRUG

Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.

Sym023 0.1 mg/kg

Sym023 was administered at a dose of 0.1 mg/kg by intravenous infusion

Group Type: EXPERIMENTAL

Sym023

Intervention Type: DRUG

Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.

Sym023 0.3 mg/kg

Sym023 was administered at a dose of 0.3 mg/kg by intravenous infusion

Group Type: EXPERIMENTAL

Sym023

Intervention Type: DRUG

Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.

Sym023 1.0 mg/kg

Sym023 was administered at a dose of 1.0 mg/kg by intravenous infusion

Group Type: EXPERIMENTAL

Sym023

Intervention Type: DRUG

Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.

Sym023 3.0 mg/kg

Sym023 was administered at a dose of 3.0 mg/kg by intravenous infusion

Group Type: EXPERIMENTAL

Sym023

Intervention Type: DRUG

Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.

Sym023 10.0 mg/kg

Sym023 was administered at a dose of 10.0 mg/kg by intravenous infusion

Group Type: EXPERIMENTAL

Sym023

Intervention Type: DRUG

Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.

Sym023 20.0 mg/kg

Sym023 was administered at a dose of 20.0 mg/kg by intravenous infusion

Group Type: EXPERIMENTAL

Sym023

Intervention Type: DRUG

Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.

Interventions

Sym023

Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.

Intervention Type: DRUG

Other Intervention Names

Anti-TIM-3

Eligibility Criteria

Inclusion Criteria

• Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.
• Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
• Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or nonresectability of the tumor.
• Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
• Measurable or non-measurable disease according to RECIST v1.1 or RECIL 2017.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug.

Exclusion Criteria

• Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug. Women of childbearing potential (WOCBP) and fertile men with WOCBP-partner(s) not using and not willing to use a highly effective method of contraception.
• Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
• Hematologic malignancies other than lymphomas.
• Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to Cycle 1/Day 1 (C1/D1) unless adequately treated and considered stable.
• Active uncontrolled bleeding or a known bleeding diathesis.
• Clinically significant cardiovascular disease or condition.
• Significant ocular disease or condition, including history of autoimmune or inflammatory disorder.
• Significant pulmonary disease or condition.
• Current or recent (within 6 months) significant gastrointestinal (GI) disease or condition.
• An active, known, or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome, requiring systemic steroids or other immunosuppressive medications.
• History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy.
• Patients with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy, with exceptions.
• Inadequate recovery from any prior surgical procedure, or having undergone any major surgical procedure within 4 weeks prior to C1/D1.
• Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Symphogen A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lillian Siu, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

South Texas Accelerated Research Therapeutics (START) Midwest

Grand Rapids, Michigan, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

NEXT Oncology

San Antonio, Texas, United States

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Sym023-01

Identifier Type: -

Identifier Source: org_study_id